French Drug Research Articles

Canadian status of "drugs to avoid" in 2017: a descriptive analysis.

The independent French drug bulletin, La revue Prescrire (henceforth Prescrire), annually releases a list of drugs to avoid. The aim of this analysis was to review the status of the 2017 list of drugs in Canada to determine whether they had been approved for marketing, their therapeutic status and whether they have been recommended for listing on public drug plans. This descriptive analysis reviewed a list of drugs compiled by Prescrire. The status of each drug in Canada was assessed through the Drug Product Database. Therapeutic ratings were obtained from the Patented Medicine Prices Review Board (PMPRB) and the formulary listing recommendation came from the Common Drug Review (CDR) or the pan-Canadian Oncology Drug Review (pCODR). For drugs without a formulary recommendation the Ontario Drug Benefit (ODB) Formulary was searched to see if the product was listed. Prescrire recommended not using 92 drugs. The PMPRB evaluated 36 of these drugs; 2 were classed as substantial improvements or breakthroughs, 3 as moderate improvements and 31 as little or no therapeutic improvement. Nine of the remaining drugs that were approved in Canada were not assessed because they were approved before 1988 (the year the PMPRB was established), 4 were approved from December 2015 onward and had not yet been reviewed by the PMPRB, and for 1 the approval date was unknown. Twenty-six of the drugs were evaluated by CDR or pCODR, of which 13 were recommended for formulary listing. Sixteen additional drugs that were not evaluated were on the ODB Formulary. Many drugs that Prescrire recommended avoiding were available in Canada. The results also highlight the diversity of the conclusions that different expert panels have reached.

The mediating role of early maladaptive schemas on relations between post-traumatic stress disorder symptom severity and illicit substance use disorder

ABSTRACTBackground: This study examines the role of Early Maladaptive Schemas (EMS) on relations between Post-traumatic stress disorder (PTSD) symptoms and illicit substance use.Objectives: We assumed that EMS play a mediating role in the pathways from PTSD symptom severity to illicit substance use.Method: We used the composite score from the Addiction Severity Index to assess illicit substance use severity, the PTSD Checklist Specific to determine PTSD symptom severity, and the Young Schema Questionnaire – Short Form, Second Edition to measure the number of hyperactivated EMS. The sample consisted of 35 patients receiving social and medical care for illicit substance use problems in three French drug centers.Results: The results showed that the number of hyperactivated EMS is an intermediate variable playing a mediating role between PTSD symptom severity and illicit substance use. Results indicating full mediation. Conclusion. Future research perspectives on this question are discussed as well as the clinical repercussions of these results on the current models of management of illicit drug users.

Modafinil: its discovery, the early European and North American experience in the treatment of narcolepsy and idiopathic hypersomnia, and its subsequent use in other medical conditions

Adrafinil, a new molecule identified by a French drug company, L. Lafon Ltd, in 1974, was found to cause a significant dose-dependent increase in motor activity in mice, without exerting peripheral sympathomimetic effects. As early as 1977–78, Michel Jouvet prescribed adrafinil to narcoleptic patients, but without consistent results. Meanwhile the kinetics of adrafinil led to the identification of an active metabolite, modafinil. In 1983, Jouvet and Bastuji prescribed modafinil to narcoleptic and idiopathic hypersomnia patients and obtained a significant decrease of excessive daytime sleepiness and sleep attacks in a majority of patients. L. Lafon Ltd was initially not interested in developing this molecule for market however, thanks to Jouvet's insistance, it decided to start clinical trials in both healthy volunteers and narcoleptic patients as well as conduct animal studies. Results were excellent and led to the use of modafinil by the French army during the Gulf War in January–February 1991, as well as to the official registration of the drug in France in 1992. Subsequent multicenter controlled clinical trials in North America confirmed the findings in Europe. Modafinil was later used to treat sleepiness, somnolence and fatigue in a large number of medical conditions.

Antidepressants during pregnancy: a French drug utilisation study in EFEMERIS cohort.

Previous studies have suggested that exposure to some antidepressants (AD) during pregnancy could be associated with an increased risk of congenital malformations and neurodevelopment disorders for the child. We conducted a study to describe the use of AD during pregnancy in France. We performed a drug utilisation study in EFEMERIS, a French cohort of pregnant women. At the time of the present study, 89,170 pregnant women, who were pregnant from 2005 to 2014 in Haute-Garonne were included. Prevalence and incidence of AD prescriptions during pregnancy, characteristics of AD users, and trends in AD use over the 10-year period were studied. During the 10-year study period, 1620 women registered in EFEMERIS (1.8%) received at least one prescription and dispensation for AD during pregnancy: 1363 during the first (1.5%), 591 during the second (0.7%), and 412 during the third (0.5%) trimester. A total of 2874 women (3.2%) got a prescription for an AD during the 3months before and/or during pregnancy; 2187 of them (76.1%) stopped AD before pregnancy or during the first trimester. Selective serotonin reuptake inhibitors represented the most prescribed class during pregnancy (1.3%). A very slight decrease in the prevalence of AD prescriptions in pregnant women over time (1.7% in 2014 vs 2% in 2005) and some variations within classes were observed. Nearly, 2% of women received antidepressant drugs during pregnancy. This assessment encourages following research on these drugs including the potential risk of neurodevelopmental disorders in children after an exposure to antidepressants during pregnancy.

Prevalence of hydroxychloroquine-induced side-effects in dermatology patients: A retrospective survey of 102patients

Our aim was to assess the prevalence of adverse effects (AEs) pertaining to the use and withdrawal of hydroxychloroquine (HCQ) in dermatological outpatients. We conducted a retrospective study between January 2013 and June 2014 that included consecutive patients currently or previously receiving HCQ seen in our department. AEs were collated using a standardized questionnaire and validated by clinical and laboratory examination. Drug causality was evaluated using the updated French drug reaction causality assessment method. The main evaluation criterion was the prevalence of AEs in which HCQ had an intrinsic imputability score of I>2. We included 102patients (93 of whom were women, with a median age of 44.5; range: 22-90years). HCQ was given for cutaneous lupus in most cases (n=70). At least one AE was reported for 55patients. Among the 91 reported AEs, 59 (65%) had an HCQ intrinsic imputability score I>2. AEs were responsible for permanent HCQ discontinuation in 19cases. Of these, 8 were unrelated to HCQ based on imputability score. The most common AEs associated with HCQ were gastrointestinal and cutaneous signs. Of the 8patients diagnosed with retinopathy, only 3 were confirmed after reevaluation. AEs associated with HCQ were reported for over 50% of patients and were responsible for permanent HCQ discontinuation in one-third of cases. A more in-depth evaluation of imputability seems necessary, particularly regarding ophthalmological symptoms, since in two thirds of cases the reasons for discontinuation were not related to HCQ.

Drug consumption rooms: Comparing times, spaces and actors in issues of social acceptability in French public debate

BackgroundIn October 2016, the first French drug consumption room (DCR) opened in Paris. We propose to examine the process through which this issue has been framed as a matter of public concern, after being ignored for almost 20 years. Our analysis of the controversy on DCRs investigates how public conversations on harm reduction evolve according to the time period (from the 1990s to the present), scale of discourse (local vs. national), and involved actors (politicians, professionals, local residents, and drug users). MethodologyOur methodology includes analyses of media content: we reviewed 1735 articles published between 1990 and 2017. Our theoretical approach is in line with the sociology “des épreuves” derived from pragmatic sociology and controversy analysis. This approach goes beyond interactionism by attempting to place situations back into broader sociological realities. We also pay special attention to governance, a political lens that focuses on local aspects of negotiations and on the implication of a variety of actors. ResultsWhile the current debate on DCRs in France draws on constraints and resources already present in the harm reduction debate of the 1980s, it also repositions itself by avoiding moral argumentation and featuring less confrontation in the professional sphere. Today, we can see that the center of this tense debate has shifted from the professional sphere to the political and residential spheres. Most often, residents advance concerns that are not directly related to drug users themselves, but that derive from their apprehension of living in a displaced and stranded neighborhood. The public conversation leaves little room for drug users, even though they are the primary stakeholders of harm reduction and play a crucial role in DCR advocacy. ConclusionOur work reveals that the controversy about DCR is the product of complex interactions between different kinds of actors harm reduction professionals, political actors at the local and national levels, local residents, and drug users. Comparing different instances of public debate reveals the specific limitations and potentials for change in French drug policy.

Shire sells cancer business to Servier

The French drug company Servier will buy Shire’s cancer-drug business for $2.4 billion. Shire’s marketed products for leukemia and pancreatic cancer represent less than 2% of the rare-disease drug company’s sales. Shire also has an experimental treatment for leukemia under review at the U.S. FDA. News of the sale comes about two weeks after Japan’s Takeda Pharmaceutical announced it was considering a bid to acquire Shire.

The reporting of harms in publications on randomized controlled trials funded by the "Programme Hospitalier de Recherche Clinique," a French academic funding scheme.

Accurate information on harms arising from medical interventions is essential for assessing benefit-risk ratios. Since 2004, there has been an extension of the Consolidated Standards of Reporting Trials statement for reporting harms data in publications on randomized clinical trials. The objective of our study was to assess the quality of this reporting from academic randomized clinical trials on drugs. We searched for articles on randomized clinical trials funded between 2004 and 2008 by the "Programme Hospitalier de Recherche Clinique." We included all published randomized clinical trials that assessed drugs. Harm-related data were extracted and compared with the Consolidated Standards of Reporting Trials Harms extension, and the space in the articles devoted to harms data was measured. In total, 37 randomized clinical trials met the inclusion criteria. The median harm score was 9/18. In 73.0% of the randomized clinical trials, the reporting of adverse events was selective. Less than 50% of articles provided information on reasons for drug discontinuation that were related to adverse events. The score and the space allocated to harms were higher in antineoplastic and immunomodulating drugs randomized clinical trials, while the median proportion of the space in the results section allocated to harms was 16.8%. In 67.6% of the articles, the space allocated to the authors' list and affiliations was greater than the space in the results section allocated to descriptions of harms. No significant improvement in the score or the space allocation was observed during the study period. Reporting of harms in French academic drug randomized clinical trials is suboptimal; moreover, this shortcoming is a critical barrier to evaluating the benefit-risk ratio of drug randomized clinical trials. Thus, the authors should be encouraged to adhere to the Consolidated Standards of Reporting Trials Harms extension.

On-the-ground application of the 'temporary recommendation for use' regulatory measure on off-label use of baclofen for alcohol dependence in France: a regional survey of community pharmacies.

The 'temporary recommendation for use' (TRU) is a French novel regulatory measure for off-label drug. The first TRU to be issued by the French drug agency (in March 2014) pertained to the off-label use of baclofen for alcohol dependence (AD). We performed a questionnaire-based survey of the on-the-ground application of the baclofen TRU among community pharmacies in northern France. A pharmacist from 70 of the 219 pharmacies contacted (response rate: 32.0%) completed the questionnaire. The mean ± standard deviation number of off-label baclofen prescriptions for AD was 2.3 ± 2.2 per pharmacy per month. 65.2% of these prescriptions were issued by primary care physicians. 65.7% of the pharmacists had never seen 'TRU' written on the prescription, and 80.3% delivered a prescription without checking whether the patient had been included by the prescriber in the TRU. The main criterion used to identify off-label prescribing was the patient's medical history (according to 74.6% of pharmacists) and the prescription of an above-threshold dose (73.1%). 87.1% of the pharmacists were aware of the baclofen TRU, and 42.9% had actually read the document. 17.9% of the pharmacists estimated that the TRU had changed their attitude to off-label baclofen prescription, and 29.9% (20 out of 67) of them wanted to be more involved in the TRU process. Community pharmacists were well informed about the off-label use of baclofen for AD and the TRU. However, a majority of baclofen prescribers did not fulfill the TRU requirements while a majority of pharmacists did not exert any control over these off-label prescriptions. In practice, in 2015 the TRU measure had thus a limited impact on both the baclofen prescribing and delivery practices.

Novartis buys French cancer drug company

Novartis will pay $3.9 billion to acquire Advanced Accelerator Applications (AAA), a French radiopharmaceutical firm that makes cancer therapies and diagnostics. AAA’s sales in the first half of 2017 were only $78 million, but analysts suggest that Novartis may replace its patent-expired cancer therapy Sandostatin—which brings in $1.6 billion per year—with AAA’s Lutathera. That therapy was recently approved in Europe to treat gastroenteropancreatic neuroendocrine tumors, the cancer that killed Apple founder Steve Jobs in 2011.

The relation between promotional spending on drugs and their therapeutic gain: a cohort analysis.

Whether drug promotion helps or hinders appropriate prescribing by physicians is debated. This study examines the most heavily promoted drugs and the therapeutic value of those drugs to help determine whether doctors should be using promotional material to inform themselves about drugs. Lists were constructed of the 50 most heavily promoted drugs (amount of money spent on journal advertisements and visits by sales representatives) and the 50 top-selling drugs (by dollar value) for 2013, 2014 and 2015. Therapeutic gain was determined by examining ratings from the Patented Medicine Prices Review Board and the French drug bulletin Prescrire International and was categorized as major, moderate or little to none. For each of the 3 years, the number of drugs in the 3 therapeutic categories for drugs in both groups was compared. The amount and proportion of money spent on promotion for drugs in each of the 3 therapeutic categories for the 3 years was also determined. Therapeutic ratings were available for 42 of 79 of the most heavily promoted drugs over the 3 years and for 40 of 61 of the top-selling drugs. Nearly all the money spent on promotion in each of the 3 years went to drugs with little to no therapeutic gain. The distribution of therapeutic gain for drugs in both groups was statistically significantly different only in 2013 (p = 0.04). Most of the money spent on promotion went to drugs that offer little to no therapeutic gain. This result calls into question whether doctors should read journal advertisements or see sales representatives to acquire information about important medical therapies.

After French drug trial tragedy, European Union issues new rules to protect study volunteers

After French drug trial tragedy, European Union issues new rules to protect study volunteers

The Measures of French Regulatory Agency for Clinical Trials Conduction After the Rennes Disaster

To show how French system reacted to the so-called “Rennes Disaster”, in which six healthy volunteers, after a fatty acid amide hydrolase inhibitor intake, presented serious brain damage and one died subsequently to these lesions. The aim of this communication was to illustrate the requirements of French Ministry of Health after the “Rennes Disaster”, and how the safety and vigilance units of academic sponsors implemented these new requirements in their routine activity. The key points of changes in French regulatory requirements were summarized. Thereafter, a focus on the actions of the Revise (REflections on VIgilance and SafEty of Clinical trials) Network was presented. The Revise Network was created on 2007, and it now federates around fifty safety units of academic sponsors. From the beginning, the majority of them were supported by a pharmacology department in the context of French regional centres of pharmacovigilance. After the Rennes Disaster, the ministry of health imposed that in all study on drugs performed on healthy subjects, every serious adverse reaction leading to hospitalisation must be considered as an emerging safety issue and reported immediately to the French Drug Safety Agency (Agence Nationale de la securité du Médicament, ANSM). The study must be interrupted immediately and, to restart with the inclusions, the sponsor must bring proof its harmlessness to ANSM. Moreover, all healthy subjects must be informed and give a new consent before any new administration. Later on, the Jardé law considered all serious adverse events observed on healthy volunteers as a safety issue and must be reported immediately to ANSM. In any other clinical trial phases, life-threatening or fatal SUSARs (suspected unexpected adverse drug reaction) must be reported without any delay to ANSM. The extreme short time to assess serious adverse events before the transmission, imposed to reinforce the organisation of vigilance units for their management. The Revise Network proposed 30 guidelines to harmonies the procedures, such as a guideline for a safety management plan tailored to the evaluation of benefit risk assessment based on clinical pharmacology expertise. The French authorities and the vigilance units promptly reacted to the Rennes Disaster. The Revise Network, university hospital directorates and the institutional pharmacology units are working together to help in better preventing and managing the safety of people included in clinical trials.

New clues to why a French drug trial went horribly wrong

New clues to why a French drug trial went horribly wrong

Drug use and addictive practices in France

In terms of drug use, legal substances, namely tobacco and alcohol, are the most commonly consumed. Cannabis is the most widely consumed illegal substance, followed by cocaine with ten times fewer users, far ahead of other products. Thisbroad overview conceals numerous nuances explored by the French drug and drug addiction watch.

Mood is bright at new drug ingredients show

Attendees at CPhI North America, the new U.S. iteration of a popular European pharmaceutical ingredients trade show, found the sector in continued exuberance. Investment has marched on, especially in the U.S., as contract development and manufacturing firms respond to demand for more capacity. And most firms reported significant sales growth. But discussion at the event, held in Philadelphia from May 16–18, was dominated by news of two acquisitions: Thermo Fisher’s plan to acquire the drug services firm Patheon for $7.2 billion (see story above) and Novacap’s agreement to buy control of the French drug ingredients maker PCAS in a deal that values PCAS at more than $250 million. Many were puzzled by the combination of Thermo Fisher, a major supplier of laboratory instruments, and Patheon. Others, though, saw the emergence of a huge “one-stop-shop” for the drug industry through the combination of Thermo Fisher’s clinical delivery business and Patheon’s manufacturing

Cost-effectiveness analysis on the use of fidaxomicin and vancomycin to treat Clostridium difficile infection in France

Background: Fidaxomicin is a macrocyclic antibiotic with proven efficacy against Clostridium difficile infection (CDI) in adults. It was licensed in France in 2012, but, due to higher acquisition costs compared with existing treatments, healthcare providers require information on its cost/benefit profile.Objective: To compare healthcare costs and health outcomes of fidaxomicin and vancomycin, as reference treatment for CDI.Methods: A Markov model was used to simulate the treatment pathway, over 1 year, of adult patients with CDI receiving fidaxomicin or vancomycin. Several patient sub-groups (severe CDI; recurrent CDI; concomitant antibiotics; cancer; renal failure; elderly) were evaluated. Cost-effectiveness was analyzed based on cure and recurrence rates derived from published randomized clinical trials comparing fidaxomicin and vancomycin, and costs calculated from the payer perspective using French hospitalization data and drug cost databases. Model outputs included costs in euros (reference year 2014) and health outcomes (recurrence; sustained cure rates). Alternative scenario and sensitivity analyses were performed using data from other clinical trials in CDI, including one conducted in real-life clinical practice in France.Results: Drug acquisition costs were €1,692 higher in fidaxomicin-treated patients, but this was offset by the lower hospitalization costs with fidaxomicin, which were reduced by €1,722. The reduction in the cost of hospitalization was driven by the significantly lower number of recurrences in fidaxomicin-treated patients, offsetting the acquisition cost of fidaxomicin in all sub-groups except recurrent CDI and concomitant antibiotics.Conclusion: This study demonstrated that, despite higher acquisition costs, the lower recurrence rate with fidaxomicin resulted in cost savings or low incremental costs compared with vancomycin.

Vigi4Med Scraper: A Framework for Web Forum Structured Data Extraction and Semantic Representation.

The extraction of information from social media is an essential yet complicated step for data analysis in multiple domains. In this paper, we present Vigi4Med Scraper, a generic open source framework for extracting structured data from web forums. Our framework is highly configurable; using a configuration file, the user can freely choose the data to extract from any web forum. The extracted data are anonymized and represented in a semantic structure using Resource Description Framework (RDF) graphs. This representation enables efficient manipulation by data analysis algorithms and allows the collected data to be directly linked to any existing semantic resource. To avoid server overload, an integrated proxy with caching functionality imposes a minimal delay between sequential requests. Vigi4Med Scraper represents the first step of Vigi4Med, a project to detect adverse drug reactions (ADRs) from social networks founded by the French drug safety agency Agence Nationale de Sécurité du Médicament (ANSM). Vigi4Med Scraper has successfully extracted greater than 200 gigabytes of data from the web forums of over 20 different websites.

Association of UV radiation with Parkinson disease incidence: A nationwide French ecologic study

BackgroundVitamin D is thought to contribute to brain health, but it is unclear whether low vitamin D levels are associated with increased incidence of Parkinson's disease (PD). Using ultraviolet B (UV-B) as a surrogate for vitamin D levels, we conducted a nationwide ecologic study in France in order to examine the association of UV-B with PD incidence. MethodsWe used French national drug claims databases to identify PD cases using a validated algorithm. UV-B data from the solar radiation database were derived from satellite images. We estimated PD incidence (2010–2012) at the canton level (small administrative French unit) and used multilevel Poisson regression to examine its association with UV-B (2005 annual average), after adjustment for age, sex, deprivation index, density of neurologists, smoking, proportion of agricultural land, and vitamin D supplementation. ResultsAnalyses are based on 69,010 incident PD patients. The association between UV-B and PD incidence was quadratic (P<0.001) and modified by age (P<0.001). Below 70y, incidence was higher in the bottom quintile (relative risk, RRQ1:45-49y=1.18, 95% CI=1.08–1.29) compared with the middle UV-B quintile, and lower in the top quintile (RRQ5:45-49y=0.85 [0.77–0.94]). An opposite pattern was observed in older subjects (RRQ1:85-89y=0.92 [0.89–0.96]; RRQ5:85-89y=1.06 [1.02–1.11]). Analysis based on continuous UV-B yielded similar conclusions. ConclusionsIn this nationwide study, there was an age-dependent quadratic association between UV-B and PD incidence. This study suggests that reasonable UV-B exposure is associated with lower PD risk in younger persons and that future studies should examine dose-response relations and take age into account.

A Death and Other Adverse Events in French Drug Trial Raise Questions About Testing Safety and Ethics

A Death and Other Adverse Events in French Drug Trial Raise Questions About Testing Safety and Ethics